TY  - JOUR
AU  - Vaidyanathan, B
AU  - Chaudhry, A
AU  - Yewdell, WT
AU  - Angeletti, D
AU  - Yen, W-F
AU  - Wheatley, AK
AU  - Bradfield, CA
AU  - McDermott, AB
AU  - Yewdell, JW
AU  - Rudensky, AY
AU  - Chaudhuri, J
Y2  - 2020/12/17
Y1  - 2017/01/01
SN  - 0022-1007
UR  - http://hdl.handle.net/11343/255399
AB  - Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool. In this study, we show that an environmental sensor, the aryl hydrocarbon receptor (AhR) is highly induced upon B cell activation and serves a critical role in regulating activation-induced cell fate outcomes. We find that AhR negatively regulates class-switch recombination ex vivo by altering activation-induced cytidine deaminase expression. We further demonstrate that AhR suppresses class switching in vivo after influenza virus infection and immunization with model antigens. In addition, by regulating Blimp-1 expression via Bach2, AhR represses differentiation of B cells into plasmablasts ex vivo and antibody-secreting plasma cells in vivo. These experiments suggest that AhR serves as a molecular rheostat in B cells to brake the effector response, possibly to facilitate optimal recall responses. Thus, AhR might represent a novel molecular target for manipulation of B cell responses during vaccination.
LA  - English
PB  - ROCKEFELLER UNIV PRESS
T1  - The aryl hydrocarbon receptor controls cell-fate decisions in B cells
DO  - 10.1084/jem.20160789
IS  - Journal of Experimental Medicine
VL  - 214
IS  - 1
SP  - 197-208
L1  - /bitstream/handle/11343/255399/PMC5206498.pdf?sequence=1&isAllowed=y
ER  -